Atul Bhan, M.D., M.B.B.S.
Physician Investigator (Cl)
Molecular Pathology Unit, Mass General Research Institute
Professor of Pathology
Harvard Medical School
Pathology, Massachusetts General Hospital
|MBBS Christian Medical College 1965|
|MD All India Institute of Medical sciences 1969|
The availability of a wide variety of experimental models of intestinal inflammation has helped provide important clues about the pathogenesis of IBD. The commonly used models include chemically induced mucosal injury and colitis induced by the transfer of selected populations of T cells into immunodeficient mice. The spontaneous development of colitis in genetically engineered animal models has provided excellent experimental models to study the pathogenesis of IBD. One important lesson learned from IBD models is that many different immunologic and mucosal defects can lead to similar pathologic findings.
For the last several years, our laboratory has focused on defining the pathogenesis of chronic intestinal inflammation using TCR alpha KO mice as a model of human IBD. TCR alpha KO mice develop spontaneously chronic colitis with many features of ulcerative colitis. We have identified a regulatory B cell subset, which appears under chronic intestinal inflammatory conditions and suppresses the progression of intestinal inflammation by secreting IL-10. TCR alpha KO mice deficient in both IL-4 and B cells, but not in IL-4 alone, develop granulomatous colitis with features of Crohn’s disease. This suggests that differences in the two major forms of IBD may reflect different immunological responses to similar initiating events.
The laboratory is closely associated with the Center for the Study of Inflammatory Bowel Disease at MGH and collaborates with the other members of the Center; Dr. Bhan is an Associate Director of the Center. In collaboration with Dr. Terhorst and Dr. Xavier we have studied the role of Th-1 and Th-17 pathways, innate immune system and autophagy in the development of intestinal inflammation. Collaborative studies with Dr. Scott Snapper’s laboratory have shown that interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. The studies with Dr. Richard Hodin’s laboratory indicate that administration of intestinal alkaline phosphatase may have a beneficial effect in intestinal inflammatory conditions and metabolic syndromes. Dr. Bhan’s consultant role in the newly established Harvard Institute of Translational Immunology-Helmsley Pilot Program in Crohn’s Disease has led to his collaboration with Dr. Vijay Yajnik at MGH and Dr. Matthew Myerson at DFCI to identify microorganisms in Crohn’s disease lesions.